Ellagic acid effects on the carcinogenicity, DNA-binding and metabolism of 7,12-dimethylbenz(a)anthracene (DMBA)

Naturally-occurring components of the human food supply have recently received attention as possible agents for cancer chemoprevention. The plant phenol ellagic acid has been reported to be an effective inhibitor of carcinogen metabolism and certain chemically-induced tumors. Therefore, we evaluated the efficacy of ellagic acid in inhibiting DMBA metabolism, DNA-binding and the initiation of DMBA-induced carcinogenesis in rat mammary tissue. Mammary epithelial cell aggregates were isolated from rats fed control and ellagic acid (0.4 and 0.8%) containing diets. When incubated with DMBA, aggregates from ellagic acid-fed rats exhibited a significant but modest inhibition of DMBA metabolism and DNA-binding. An inhibition of DMBA-DNA binding and DMBA metabolism in secondary cultures of mammary epithelial cells also was detected only when ellagic acid was added at 150 molar excess compared to DMBA. The feeding of ellagic acid (0.8%) to rats for 28 days prior to the administration of DMBA resulted in a 21% reduction in mammary tumor incidence at 21 weeks which was, however, not statistically significant. Together, these results indicate that, in contrast to its effects with other carcinogens in other tissues, ellagic acid is not a potent inhibitor of DMBA metabolism, DNA-binding and carcinogenicity with rat mammary tissue.